This invention relates to a method of preparing monopotassium L-malate and its monohydrate.
Potassium is an important cationic constituent in living bodies and a potassium salt of the L-malic acid is useful in the treatment of hypo-potassemia.
It is known in the art that the hygroscopic character of dipotassium DL-malate makes it difficult to prepare and store said salt in solid form. In order to improve the hygroscopicity of dipotassium DL-malate, attempts have been made to prepare the corresponding monohydrate. For example, U.S. Pat. No. 3,435,070 discloses that dipotassium DL-malate monohydrate is prepared by adjusting the pH of an aqueous DL-malic acid solution to between 7.0 and 9.0 with potassium carbonate, concentrating the solution at a temperature of at least 110.degree. C., and then cooling the concentrated solution to below about 30.degree. C. Alternatively, Japanese Patent Application No. 76,518/1975 (laid open to the public under No. 3,019/1977) discloses that dipotassium DL-malate monohydrate is prepared by reacting DL-malic acid with potassium hydroxide in an aqueous alcohol, adjusting the pH of the reaction solution to between 7 and 9.5, and then recovering the precipitates therefrom. However, dipotassium L-malate and its monohydrate are highly soluble in water and can not be obtained as crystals by these known methods even by employing L-malic acid instead of DL-malic acid as the starting material.
In addition to the above-mentioned methods, an aqueous solution of monopotassium L-malate may be obtained by mixing L-malic acid with an equimolar amount of potassium ion in water. However, monopotassium L-malate is different from the corresponding sodium salt and monopotassium DL-malate with respect to their crystallographic properties and it is impossible to recover the pure crystals of monopotassium L-malate from said aqueous solution by conventional methods. For example, the crystals which are recovered from said aqueous solution by refrigeration and/or concentration are composed of one mole of L-malic acid and between about 0.6 and 0.8 mole of potassium ion.